The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug.
The 'Switch' study protocol: a randomised-controlled trial of switching to an alternative tumour-necrosis factor (TNF)-inhibitor drug or abatacept or rituximab in patients with rheumatoid arthritis who have failed an initial TNF-inhibitor drug.
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DOI：
10.1186/1471-2474-15-452
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发表时间：
2014-12-23
影响因子：
2.3
通讯作者：
Buch MH
中科院分区：
文献类型：
--
作者：
Navarro Coy NC;Brown S;Bosworth A;Davies CT;Emery P;Everett CC;Fernandez C;Gray JC;Hartley S;Hulme C;Keenan AM;McCabe C;Redmond A;Reynolds C;Scott D;Sharples LD;Pavitt S;Buch MH
风湿性关节炎（RA）是最常见的自身免疫性疾病之一，影响约1%的英国成年人口。患者遭受相当大的疼痛、僵硬和肿胀，并且可以承受不同程度的关节破坏、畸形和显著的功能下降。此外，住院和失业造成的经济负担相当大，超过50%的患者在诊断后10年内丧失工作能力。尽管现在有几种生物疾病修饰抗风湿药物（bDMARD），但缺乏指导生物测序的数据。在英国，二线生物治疗仅限于单一选择，利妥昔单抗。该试验的目的是确定替代机制TNF抑制剂（TNFi）或阿巴西普是否与初始TNFi药物失败的RA患者中的利妥昔单抗一样有效。ESTA是一个务实的，IV期，多中心，平行组设计，开放标签，随机对照试验（RCT）比较替代机制TNFi和阿巴西普与利妥昔单抗在RA患者谁失败的初始TNFi药物。参与者以1：1：1的比例随机分配，在干预阶段（从随机化到第48周）接受替代机制TNFi（单克隆抗体：英夫利昔单抗、阿达木单抗、赛妥珠单抗或戈利木单抗或受体融合蛋白依那西普）、阿巴西普或利妥昔单抗。随后对参与者进行最长96周的随访，这构成了观察期。主要目的是确定替代机制-TNFi或阿巴西普在随机化后24周的疾病应答方面是否不劣于利妥昔单抗。次要目的包括比较替代机制TNFi和阿巴西普与利妥昔单抗在12个月期间（48周）的疾病反应，生活质量，毒性，安全性和结构和骨密度结果方面的差异，并评估与当前实践相比，将患者转换为替代活性治疗的成本效益。该试验是该治疗领域的一项精心设计的试验，旨在开发合理的治疗算法，以潜在地为个性化治疗方案提供信息（而不是将所有患者仅转换为一种可用（可能不成功）的治疗），这可能导致长期改善患者结局并改善人群健康。UKCRN投资组合ID：12343; ISRCTN 89222125; NCT 01295151本文的在线版本（doi：10.1186/1471-2474-15-452）包含补充材料，可供授权用户使用。
Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases, affecting approximately 1% of the UK adult population. Patients suffer considerable pain, stiffness and swelling and can sustain various degrees of joint destruction, deformity, and significant functional decline. In addition, the economic burden due to hospitalisation and loss of employment is considerable, with over 50% of patients being work-disabled within 10 years of diagnosis. Despite several biologic disease modifying anti-rheumatic drugs (bDMARD) now available, there is a lack of data to guide biologic sequencing. In the UK, second-line biologic treatment is restricted to a single option, rituximab. The aim of the SWITCH trial is to establish whether an alternative-mechanism-TNF-inhibitor (TNFi) or abatacept are as effective as rituximab in patients with RA who have failed an initial TNFi drug. SWITCH is a pragmatic, phase IV, multi-centre, parallel-group design, open-label, randomised, controlled trial (RCT) comparing alternative-mechanism-TNFi and abatacept with rituximab in patients with RA who have failed an initial TNFi drug. Participants are randomised in a 1:1:1 ratio to receive alternative mechanism TNFi, (monoclonal antibodies: infliximab, adalimumab, certolizumab or golimumab or the receptor fusion protein, etanercept), abatacept or rituximab during the interventional phase (from randomisation up to week 48). Participants are subsequently followed up to a maximum of 96 weeks, which constitutes the observational phase. The primary objective is to establish whether an alternative-mechanism-TNFi or abatacept are non-inferior to rituximab in terms of disease response at 24 weeks post randomisation. The secondary objectives include the comparison of alternative-mechanism-TNFi and abatacept to rituximab in terms of disease response, quality of life, toxicity, safety and structural and bone density outcomes over a 12-month period (48 weeks) and to evaluate the cost-effectiveness of switching patients to alternative active therapies compared to current practice. SWITCH is a well-designed trial in this therapeutic area that aims to develop a rational treatment algorithm to potentially inform personalised treatment regimens (as opposed to switching all patients to only one available (and possibly unsuccessful) therapy), which may lead to long-term improved patient outcomes and gains in population health. UKCRN Portfolio ID: 12343;ISRCTN89222125;NCT01295151 The online version of this article (doi:10.1186/1471-2474-15-452) contains supplementary material, which is available to authorized users.
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影响因子：
4.9
作者：
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通讯作者：
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158.5
作者：
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通讯作者：
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作者：
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通讯作者：
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